Our aim is to describe a new inherited retinal disease, presumed to be degenerative, in mice homozygous for the cribriform degeneration (cri) mutation. The disease has features in common with certain forms of human retinitis pigmentosa, but of greater immediate relevance, it offers an opportunity, when studied in relation to the several other available inherited retinal diseases in mammals, to deepen our understanding of photoreceptor cell development and function. The cri disease differs from any of the others in that it seems to affect some classes of neurons in the inner nucleus layer of the retina, in addition to the photoreceptors. This provides a very special opportunity to come to know more in mammals about the relatively inaccessible transsynaptic interactions that presumably occur among photoreceptor, bipolar, and horizontal cell neurons. As a first step, we plan to develop a very detailed and careful description of the morphological disorder in the mutant retina at all stages of the disease from postnatal day 10 (P10) to P60. Light and electron microscopic methods will be applied. With the aid of an elaborate computer graphics hardware and software system now in operation in our department, we plan to count the numbers and measure the sizes of each major class of retinal neuron and glial cell as a function of postnatal age. Delineation and cunting of some of the retinal cell types will require special methods, such as retrograde labeling of ganglion cell neurons and selective immunocytochemical staining of horizontal neurons. A new autoradiographic method will be developed and applied to quantifying daily rates of cell genesis and cell death. The unusual delay in the lengthening of rod outer segments will be analyzed rinetically by autoradiography and analytical chemistry to determine if low synthesis or high degradation rates are responsible. Several formal genetics experiments will be done, to map the gene responsible for the retinal disorder in contradistinction to other aspects of the present phenotype, to determine intrinsic versus extrinsic action of the cri gene through the use of chimeras, and to produce double mutants and new congenic strains that will open up the study of regulator genes affecting photoreceptor cell development.